TY  - JOUR
AU  - Hermone, Ann R.
AU  - Burnett, James C.
AU  - Nuss, Jonathan E.
AU  - Tressler, Lyal E.
AU  - Nguyen, Tam L.
AU  - Šolaja, Bogdan A.
AU  - Vennerstrom, Jonathan L.
AU  - Schmidt, James J.
AU  - Wipf, Peter
AU  - Bavari, Sina
AU  - Gussio, Rick
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/593
AB  - A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - ChemMedChem
T1  - Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore
VL  - 3
IS  - 12
SP  - 1905
EP  - 1912
DO  - 10.1002/cmdc.200800241
ER  - 

@article{
author = "Hermone, Ann R. and Burnett, James C. and Nuss, Jonathan E. and Tressler, Lyal E. and Nguyen, Tam L. and Šolaja, Bogdan A. and Vennerstrom, Jonathan L. and Schmidt, James J. and Wipf, Peter and Bavari, Sina and Gussio, Rick",
year = "2008",
abstract = "A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "ChemMedChem",
title = "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore",
volume = "3",
number = "12",
pages = "1905-1912",
doi = "10.1002/cmdc.200800241"
}

Hermone, A. R., Burnett, J. C., Nuss, J. E., Tressler, L. E., Nguyen, T. L., Šolaja, B. A., Vennerstrom, J. L., Schmidt, J. J., Wipf, P., Bavari, S.,& Gussio, R.. (2008). Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem
Wiley-V C H Verlag Gmbh, Weinheim., 3(12), 1905-1912.
https://doi.org/10.1002/cmdc.200800241

Hermone AR, Burnett JC, Nuss JE, Tressler LE, Nguyen TL, Šolaja BA, Vennerstrom JL, Schmidt JJ, Wipf P, Bavari S, Gussio R. Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem. 2008;3(12):1905-1912.
doi:10.1002/cmdc.200800241 .

Hermone, Ann R., Burnett, James C., Nuss, Jonathan E., Tressler, Lyal E., Nguyen, Tam L., Šolaja, Bogdan A., Vennerstrom, Jonathan L., Schmidt, James J., Wipf, Peter, Bavari, Sina, Gussio, Rick, "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore" in ChemMedChem, 3, no. 12 (2008):1905-1912,
https://doi.org/10.1002/cmdc.200800241 . .

TY  - JOUR
AU  - Burnett, James C.
AU  - Opsenica, Dejan M.
AU  - Sriraghavan, Kamaraj
AU  - Panchal, Rekha G.
AU  - Ruthel, Gordon
AU  - Hermone, Ann R.
AU  - Nguyen, Tam L.
AU  - Kenny, Tara A.
AU  - Lane, Douglas J.
AU  - McGrath, Connor F.
AU  - Schmidt, James J.
AU  - Vennerstrom, Jonathan L.
AU  - Gussio, Rick
AU  - Šolaja, Bogdan A.
AU  - Bavari, Sina
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/828
AB  - We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC(50)'s ranged from 3.2 to 17 mu M). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease
VL  - 50
IS  - 9
SP  - 2127
EP  - 2136
DO  - 10.1021/jm061446e
ER  - 

@article{
author = "Burnett, James C. and Opsenica, Dejan M. and Sriraghavan, Kamaraj and Panchal, Rekha G. and Ruthel, Gordon and Hermone, Ann R. and Nguyen, Tam L. and Kenny, Tara A. and Lane, Douglas J. and McGrath, Connor F. and Schmidt, James J. and Vennerstrom, Jonathan L. and Gussio, Rick and Šolaja, Bogdan A. and Bavari, Sina",
year = "2007",
abstract = "We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC(50)'s ranged from 3.2 to 17 mu M). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease",
volume = "50",
number = "9",
pages = "2127-2136",
doi = "10.1021/jm061446e"
}

Burnett, J. C., Opsenica, D. M., Sriraghavan, K., Panchal, R. G., Ruthel, G., Hermone, A. R., Nguyen, T. L., Kenny, T. A., Lane, D. J., McGrath, C. F., Schmidt, J. J., Vennerstrom, J. L., Gussio, R., Šolaja, B. A.,& Bavari, S.. (2007). A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 50(9), 2127-2136.
https://doi.org/10.1021/jm061446e

Burnett JC, Opsenica DM, Sriraghavan K, Panchal RG, Ruthel G, Hermone AR, Nguyen TL, Kenny TA, Lane DJ, McGrath CF, Schmidt JJ, Vennerstrom JL, Gussio R, Šolaja BA, Bavari S. A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease. in Journal of Medicinal Chemistry. 2007;50(9):2127-2136.
doi:10.1021/jm061446e .

Burnett, James C., Opsenica, Dejan M., Sriraghavan, Kamaraj, Panchal, Rekha G., Ruthel, Gordon, Hermone, Ann R., Nguyen, Tam L., Kenny, Tara A., Lane, Douglas J., McGrath, Connor F., Schmidt, James J., Vennerstrom, Jonathan L., Gussio, Rick, Šolaja, Bogdan A., Bavari, Sina, "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease" in Journal of Medicinal Chemistry, 50, no. 9 (2007):2127-2136,
https://doi.org/10.1021/jm061446e . .